Protonation regioselectivity

A more complex cumulenyl carbenoid 80 may be generated in situ from 1,4-dihalobut-2-ynes and two equivalents of base (Scheme 3.21). Insertion into organozirconocene chlorides gives allenyl zirconium species 81, which are regioselectively protonated to afford enyne products 82 [38], The stereochemistry of the alkene in 82 stems from the initial elimination of hydrogen chloride to form 80. 

By means of in situ NMR spectroscopy combined with deuterium incorporation experiments, van Leeuwen has elucidated the mechanism of termination by protonolysis, showing that the fl-chelates are in equilibrium with their enolate form by a p-H elimination/hydride migration process (Scheme 7.19). The enolate intermediates are regioselectively protonated at the C2 carbon atom by either MeOH or H2O to give Pd-OMe or Pd-OH and keto terminated copolymer. The enolate formation has been reported to be rate determining in the chain transfer [19]. 

The high selectivities found in the protonation experiments of the nitronate ions 44 suggested that also allyl anions 54 can be regioselectively protonated by a general acid protonation. Therefore, some lithium allyl compounds (Structures 6) were generated by deprotonation of alkenes with n-butyl lithium. 

Intramolecular hydroamination of cyclohexa-2,5-dienes has afforded the corresponding bicyclic allylic amines with high selectivity (Scheme 13).80 The reaction does not proceed through a direct hydroamination of one of the diastereotopic alkenes but more likely involves a diastereoselective protonation of a pentadienyl anion, followed by addition of a lithium amide across the double bond of the resulting 1,3-diene and a highly regioselective protonation of the final allylic anion. 

The mechanism does not proceed through a direct hydroamination of one of the diastereotopic alkenes, but involves a series of very selective processes including a deprotonation of (22), diastereoselective protonation of (26), intramolecular addition of lithium amide (27) to the 1,3-diene moiety, and final regioselective protonation of the allyl anion (28), all mediated by a substoichiometric amount of n-BuLi. 

Acid-catalyzed addition of methanol to the glycal proceeds by regioselective protonation of the dou-... 

Reaction (5.12) shows an example of a reductive opening of a benzylidene. The mixture of the acetal and sodium cyanoborohydride (NaBHjCN) in oxolane is acidified with HCI in ether until no more gas is emitted. The reaction, which appears to be general (Garegg et al. 1982), is completed in 5 min at room temperature in 87% yield. This can be interpreted as resulting from regioselective protonation at 0-4 of the sugar, followed by displacement of oxonium by a hydride. 

Acid-catalyzed addition of methanol to the glycal proceeds by regioselective protonation of the double bond in the direction that leads to the more stable carbocation. Here again, the more stable car-bocation is the one stabilized by the ring oxygen. 

Figure 32. The regioselective protonation of alkyne complexes, leading to stereoselective formation of cis or /rans-alkenes.

General and specific protonations are discussed in U. Luning, C. Wangnick, M. Kiimmerlin, Regioselective protonation of aUyUithinm compounds, Chem. Ber., 1994, 127, 2431-... 

The pentacyclic triterpene skeleton hopane is generated by 2,7-, 6,11-, 10,15-, 14,19-, and 18,22-cyclization of the carbenium ion in a fivefold chair conformation (as drawn) arising from regioselective protonation of the 2,3-double bond of squalene (but not of the 2,3-epoxide). This explains why hopanes are usually not hydroxylated in the 3-position. 

Highly regioselective proton abstractions may result when sub-... 

Regioselective Protonation of Enolates. In a study of the regioselectivity of protonation of allenyl enolates, pivalic acid demonstrated superior selectivity in the example shown (eq 2), allene 1, resulting from protonation at C-2, was formed exclusively when the intermediate enolate was quenched with pivalic acid at-80°C. ... 

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